IE32509L - Naphthacene derivatives - Google Patents

Abstract

1,212,460. Daunorubicin derivatives. RHONE-POULENC S.A. 27 Nov., 1968 [28 Nov., 1967], No. 56387/68. Heading C2A. Novel daunorubicin derivatives of Formula I wherein R 1 is oxygen or a group of formula in which R 4 is H or optionally substituted alkyl, alkanoyl, thioalkanoyl, aryl, aroyl, carbamoyl, thiocarbamoyl or amidino, and R 5 is H, or R 4 and R 5 together with the common N atom form a piperazin-1-yl group having an optionally substituted alkyl radical on the second N atom, R 2 H, alkyl, aryl, aralkyl, heterocyclic, heterocyclylalkyloran optionally N-substituted aminoalkyl group and R 3 is H, or R 2 and R 3 together are a straight or branched C 3 -C 6 alkylene group, and salts thereof, are prepared by reacting an amino-acid of formula with a compound of Formula II or an acid addition salt thereof, R 1 , R 2 and R 3 being as defined above. The group of formula may be introduced before or after the reaction of daunorubicin (i.e. the compound of Formula II when R 1 is oxygen) with the amino-acid, by treatment with the appropriate hydrazine, e.g. by heating in an organic solvent. The amino acid preferably has the carboxyl group activated, e.g. by esterification with hydroxylated compounds, and the amino group protected, e.g. by a trityl or t-butoxycarbonyl group, or the N-carboxyanhydride may be used. Alternatively the reaction may be carried out in the presence of an N,N<SP>1</SP>-carbodiimide, preferably together with an organic base. The salts may be acid addition salts, or of metals or nitrogenous bases, or may be quaternary ammonium salts. Pharmaceutical compositions having antitumour properties, are in conventional forms for oral, parenteral or rectal administration and comprise the active antibiotic ingredient of Formula I above or a non-toxic salt thereof together with a pharmaceutically acceptable carrier. [GB1212460A]